Evaluation of influence of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin in rats and mice

Abstract

Background: Canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. However, drug interactions with canagliflozin can affect its glucoselowering therapeutic effects or exacerbate its adverse effects. Telmisartan, an angiotensin receptor blocker (ARB), has been approved for the treatment of diabetic kidney disease. This study aimed to investigate the effects of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry method was successfully validated to determine the levels of canagliflozin in the plasma and tissues. The main pharmacokinetic parameters were calculated using the non-compartmental model. Results: Compared with animals administered canagliflozin alone, the area under the receiver operating characteristic curve of animals co-administered telmisartan and canagliflozin was significantly increased after a single-day administration, but significantly decreased after a seven-day treatment regimen (both P<0.05). The highest concentrations of canagliflozin were detected in the kidneys, followed by the intestine, liver, heart, lung, spleen, and brain tissues. Furthermore, the concentration of canagliflozin in the heart, liver, lung, and kidney tissues at 2 hours post-administration was significantly higher in the telmisartan and canagliflozin group compared to the group treated with canagliflozin alone (P<0.05). Conclusions: A pharmacokinetic drug-drug interaction between telmisartan and canagliflozin might occur during drug co-administration.

Pharmacokinetics of cyproheptadine hydrochloride in mice and beagle dogs, tissue distribution, and excretion properties of cyproheptadine hydrochloride in mice

“…In the pharmacokinetic study, we referred to related literature to use the beagle dog to complete the drug-time curve. [22][23][24] In the establishment and validation of the assay, we used the microblood sampling method, [25][26][27] leading to good specificity in the established LC-MS/MS method and to ensure the study of pharmacokinetics. However, the limitation of this study is that the specific metabolites of CYP have not been probed in depth.…”

Intestinal Absorption of Nanoparticles to Reduce Oxidative Stress and Vasoconstriction for Treating Diabetic Nephropathy

“…At the same time, CAN and Tel can reduce the oxidative stress level by activating AMPK. , The synergistic effect of CAN and Tel can reduce blood glucose, blood pressure, and proteinuria. However, the poor solubility, low oral absorption, and renal accumulation still limit the efficacy of DN. , Therefore, it is of great significance to find new drug delivery systems.…”

“…However, the poor solubility, low oral absorption, and renal accumulation still limit the efficacy of DN. 25,26 Therefore, it is of great significance to find new drug delivery systems. Nanodelivery systems have become a research hotspot in recent years due to their characteristics of easy functional modification, improved solubility, and size control.…”